11.01.2012
Primary Chemo-Radiotherapy in the
Treatment of Locally Advanced and
Inflammatory Breast Cancer
Tom Bates 1, Nicholas J Williams 1, Susan Bendall1, E Eryl Bassett2
and R Stewart Coltart 3
The Breast Unit1, William Harvey Hospital, Ashford, Kent. TN24 OLZ UK.
The School of Mathematics, Statistics & Actuarial Science2, University of Kent.
The Department of Oncology3, Kent and Canterbury Hospital, Canterbury, Kent, UK.
Author for correspondence: Mr T Bates, Lamplands, East Brabourne, Ashford, Kent.
TN25 5LU
01233 750304
fax 01233 750599
bates.tom@virgin.net
Poster presentation: Association of Breast Surgery 17/05/2011. EJSO 2011; 37: S22
Not funded.
1
Abstract
Background.
The best management of large, diffuse or inflammatory breast cancers is uncertain
and the place of radiotherapy and/or surgery is not clearly defined.
Methods.
A cohort of 123 patients with non-metastatic locally advanced or inflammatory breast
cancer 3 cm or more in diameter or T4, was treated between 1989 and 2006. All
patients received primary chemotherapy followed by radiotherapy, 40 Gy in 15
fractions with 10 Gy boost. Patients with ER positive tumours received Tamoxifen.
Assessment was carried out 8 weeks post-treatment and surgery was reserved for
residual or recurrent disease.
Results.
For each stage there were T2/3: 63, T4b: 31 and T4d: 29 patients. 80 had complete
clinical response (65%) but 18 patients were never free of inoperable local disease. 25
patients had residual operable disease at assessment and 12 patients who initially had a
complete response developed operable local recurrence (LR). 37 patients (30%) had
surgery at a mean of 15 months post diagnosis.
At 5 years, overall survival (OS) of
the two surgical groups was not significantly different from those 68 patients who had
complete remission without surgery, p=0.218 HR 1.46 (0.80-2.55). Surgery as an
independent variable to predict survival was not significant on a Cox proportional
hazards model (p=0.97)
. LR in the surgical groups was 13.5% v. 17.5% in the non-surgical patients. The
median OS was 64.5 months and disease free survival (DFS) was 52.5 months. 5-year
OS was 54% and DFS survival 43%.
2
Conclusion.
In patients with a complete or partial response to chemo-radiotherapy for locally
advanced or inflammatory breast cancer, reserving surgery for those with residual or
recurrent local disease did not appear to compromise survival. This finding would
support examination of this treatment strategy by a randomised controlled trial
Keywords
inflammatory breast neoplasms; radiation therapy; chemotherapy; tamoxifen; cohort
studies.
Introduction
Neo-adjuvant chemotherapy has become an acceptable standard of care for the
management of locally advanced and inflammatory breast cancer in the expectation
that the downsized tumour may be more amenable to breast conserving surgery.1 Post
operative radiotherapy is then recommended to reduce the risk of local recurrence.
There has also been a trend to treat primary breast cancers of 3 cm or more in
diameter with primary chemotherapy especially where the lesion is Grade III, heavily
node positive or in a young woman, although this may not improve the outcome.2
Pre-operative chemotherapy increases the rate of breast conserving surgery3 but
complete pathological remission remains low and this may not improve overall
survival 2,4,5 although one long-term study does show survival benefit.6
For inflammatory breast cancer there is general agreement that surgery is not
appropriate primary treatment but mastectomy and post-operative radiotherapy have
been recommended when there has been a complete response to chemotherapy.7
However, Bonadonna’s group in 1981 reported a randomised trial of chemotherapy
followed by surgery or radiotherapy in locally advanced breast cancer and found no
3
difference in the outcome 8 and there are several subsequent reports of primary chemoradiotherapy in the management locally advanced and inflammatory tumours.9,10,11
The combination of chemotherapy and radiotherapy, given either concurrently or
sequentially, is now the standard of care for locally advanced cancer of the naso &
oropharynx12, oesophagus13, cervix14 and anal canal15 with subsequent salvage surgery
where necessary. There are a number of studies in breast cancer patients where
radiotherapy has been given in combination with chemotherapy but any subsequent
surgery has been reserved for those cases with residual or recurrent local disease.16
This latter management strategy, although unconventional in the management in breast
cancer has been followed in this breast unit and the outcome of a cohort of patients
with large, diffuse or inflammatory tumours, treated with primary sequential
chemotherapy, radiotherapy and hormone therapy is presented.
Method
The period of study was from January 1st 1989 to June 31st 2006. Patients were
identified from the prospective breast unit database with near complete follow up, and
further data were sourced from the oncology, and pathology databases, as well as the
case notes. Ethical approval was obtained for the retrospective study.
Patients with a biopsy proven invasive breast cancer were clinically staged according
to the TNM classification. Those patients with a tumour 3 cm or more in diameter
(T2/3) or had a diffuse (T4b) or an inflammatory carcinoma (T4d) and whose clinical
node status was N0 or N1, were treated with primary chemo-radiotherapy. Axillary
node status was determined by clinical examination, NX.
Those who presented with
metastatic disease or who developed metastases within 3 months of diagnosis were
excluded from the study.
4
Patients received chemotherapy according to the local protocol at the time.
In the
early part of the study 4 patients received a CMF regime, cyclophosphamide
500mg/m2, 5 FU 500mg/m2 & methotrexate 35mg/m2 intravenously on day 1 & 8 with
a 28 day cycle.
All subsequent patients received an anthracycline based
chemotherapy, with either
six cycles of AC, cyclophosphamide 600mg/m2 &
adriamycin 60 mg/m2 with a 21 day cycle or FEC(75), 5FU 600mg/m2, epirubicin 75
mg/m2 & cyclophosphamide 600mg /m2 with a 21 day cycle. Nine patients received
only 4 cycles of AC.
Following chemotherapy, radiotherapy was administered,
tailored to the individual patient. The majority of patients received a total dose of 40
Gy in 15 fractions over 3 weeks with a mini-tangent boost to the tumour site of 10Gy
in 10 fractions in 1 week. The axilla was included with the breast fields as per local
protocol but the supraclavicular fossa was not irradiated routinely. From 1989 all
patients were simulated for treatment planning and CT simulation was used from 2001.
3D planning and IMRT were not routinely used within the study period but the
planning techniques were considered standard UK practice at the time.
All patients
with ER positive tumours were treated with adjuvant tamoxifen with the exception of
two postmenopausal women who received an aromatase inhibitor. Three patients with
ER negative tumours and 5 with unknown receptor status also received tamoxifen.
Four pre-menopausal patients received goserelin in addition to tamoxifen. No patient
received trastuzumab as primary therapy which was not available at the time of the
study. At 6 to 8 weeks following completion of treatment, patients were assessed
clinically and radiologically by mammography and ultrasound examination, and with
typically 6 ultrasound or clinically guided biopsies of the tumour site.
When there
was no residual tumour on imaging, multiple freehand core biopsies were taken from
the site in the breast of the original tumour.
Patients then underwent three monthly
follow-up with clinical examination and annual radiological surveillance.
Delayed
5
primary surgery was reserved for residual disease at the time of treatment assessment
or for patients who subsequently developed local recurrence which was amenable to
operative intervention.
Statistical Methods
Overall and disease-free survival was calculated by the Kaplan-Meier method and
compared by the log rank test, (MedCalc, Schoonjans 2005). Potential prognostic
factors and survival were examined by a Cox model analysis.
Results
There were 123 female patients and the mean age at presentation was 50.6
years (range 27-73). The mean and age ranges for the tumour stages were T2: 51.4,
(35-72), T3: 48.1, (27-71), T4b: 51.5, (33-65), T4d: 53.5, (28-73). There were only 12
patients over the age of 65 (10%).
Over the same period 2652 patients with breast
cancer were treated with a mean and median age of 62. The tumour characteristics are
shown in Table 1. The mean length of follow up of the 55 survivors was 103 months
and the mean follow-up of all cases was 71 months.
Eighty patients were apparently free of systemic and local disease at posttreatment assessment (65%) but of these, 24 subsequently developed local recurrence
of whom 12 were operable and were treated by delayed surgery at a mean of 27.7
months (median 20). Sixty-eight patients had a complete clinical remission (55%) and
were managed without surgery, apart from one patient who requested prophylactic
mastectomy with complete pathological remission. Fig.1.
6
Core biopsy by protocol was not carried out in 29 patients (25%) and the
absence of residual disease relied on clinical examination and imaging. Thirty-eight
patients (33%) were found to have residual disease on post-treatment core biopsy and a
further 5 had evidence of progressive disease. Of these 43 patients, 18 had progressive
inoperable disease and 25 patients had operable residual disease and underwent
subsequent primary surgery, 4 by wide local excision and the remainder by
mastectomy at a mean of 9.2 months (median 9 months) post diagnosis.
Local
recurrence in the surgical groups was 13.5% v. 17.6% in non-surgical patients.
Concurrent regional recurrence was respectively 2.7% v. 4.4%. Fig.1
Eight patients (6.5%) died with uncontrolled local disease, four of whom had
an inflammatory cancer, T4d and two a diffuse tumour T4b. Seven of these patients
had progressive disease from the outset but one initially had a complete clinical
remission
Overall survival at 5 years was 54%, median 64.5 months and recurrence-free
survival was 43%, median 52.5 months. Survival analysis following local treatment
failure and salvage surgery (n=37) showed no significant difference in overall survival
between those patients who had surgery for residual local disease at post-treatment
assessment (n=25) and those with subsequent recurrent disease (n=12). p=0.646 HR
1.31 95% CI. (0.42-3.95). Fig 2. There was no significant overall survival advantage
to those patients treated by surgery compared with those who had a complete clinical
remission and no operation (n=68) p=0.218 HR 1.47 (0.81-2.55). Fig 3, or in disease
free survival p=0.18 HR 1.49 (0.84-2.55). Those patients with inoperable progressive
disease at post treatment assessment (n=18) had poor overall survival, 11% at 5 years.
Fig 4. On comparison of those patients with (37) or without (86) salvage surgery, the
tumour stage, grade, age, node and ER status were similar. A Cox proportional
hazards model which excluded those patients with progressive disease, was used to
7
assess whether surgery could be viewed as an independent variable to predict survival
but the result was not significant (p=0.97).
There was no significant difference in survival in patients who were clinically
node positive (n=44) compared with those who were node negative (n=79) p = 0.28
95% C.I. (0.4-1.3). Pathological node status was not available. (pNx: n=123)
Survival in patients who were oestrogen receptor (ER) positive (49%) was
significantly improved compared with those who were ER negative p=0.028 HR 1.79
CI (1.06-3.13).
Patients with Grade III tumours (57%) had a marginally worse
survival than those with Grade II tumours but this was not statistically significant.
P=0.076, HR 0.61, 95% CI (0.36-1.05).
There was no significant difference in survival by T-stage, T2/T3 v T4
p=0.29 HR 0.775 CI (0.48-1.25). Fig 7. T2 v T3 p=0.114 HR 1.73 CI (0.86- 3.78).
T4b v T4d p= 0.96 HR 1.01 CI (0.52-1.95). Fig 5b.
Patients aged less than 40,
(n=21) showed no difference in survival from older patients. p=0.47 HR 1.25 CI
(0.66-2.45) or on age by decade.
Of 68 deaths, 58 were certified as due to breast cancer, 6 as not due to breast cancer
and breast cancer was not present and 4 were uncertain or unknown.
Discussion
The aim of this study was to assess the outcome of patients treated with primary
sequential chemo-radiotherapy, and to assess the role that any subsequent surgery
played in maintaining local control of the disease. Primary chemoradiotherapy is now
8
standard practice for tumours of the nasopharynx, oesophagus, cervix and anus 12-15
with reservation of surgery for residual or recurrent disease and this policy may be
adopted for some rectal cancers.17 Many breast cancers are sensitive to chemotherapy
and or radiotherapy and yet this treatment modality is not widely used.
The number of patients is relatively small but over the period of study confidence in
this unconventional treatment strategy gradually increased. In the early years breast
referrals to the unit were lower and latterly the incidence of locally advanced breast
cancer appears to have fallen with the advent of the screening programme in the UK
which started in 1988.
The complete clinical remission rate of 65% in patients with locally advanced or
inflammatory breast cancer after chemo-radiotherapy is higher than would be expected
after neo-adjuvant chemotherapy alone. However if all patients had had immediate
surgical treatment post therapy, as would be the case with neo-adjuvant chemotherapy,
the remission rate would probably have been lower since some of the post treatment
core biopsies may have been false negative. Subsequent local recurrences would have
been apparent at earlier stage as residual disease. Nevertheless, if all 24 subsequent
local recurrences are taken as residual disease the complete remission rate would have
been 45% in this poor-risk group of patients.
. The locoregional recurrence rate of 13.5% in the surgical patients and 17.5% in the
non-surgical group is high but no more than would be expected from a recent large
study.18
86 patients (70%) avoided any surgery although of these 12 had a local
recurrence which was not amenable to subsequent salvage surgery. It is therefore
possible that as many as twelve patients (10%) may have been disadvantaged by the
lack of primary surgery. Against this must be considered the poor prognosis of this
group of patients with locally advanced disease, half of whom had diffuse or
9
inflammatory tumours 7, 19,20,21,22,23 and as expected, the greatest risk to overall survival
was the progression to metastatic disease rather than local recurrence. There was no
evidence of survival benefit from surgery on multivariate analysis and there is
therefore no support from this study for surgery having an independent effect on
survival.
Walshe21 has suggested that inflammatory breast cancer is a distinct disease entity
although Montagna et al23 found no difference in recurrence free or overall survival
between inflammatory and non-inflammatory breast cancer, Another large study from
the MD Anderson22 reported that that the outcome from inflammatory cancers was
significantly worse and this finding has been supported by a subsequent analysis of
SEER data.24 There was no significant difference in outcome in the present study
when such tumours were compared with those which were designated as advanced on
the basis of size and although there was a trend for the diffuse and inflammatory
cancers to fare worst the difference was not significant 24 patients had T2 tumours 3 to
5cm in diameter which were nevertheless judged to be locally advanced on clinical
grounds. This small group had a non-significantly worse outcome than those with T3
tumours (Fig 5b)
The lack of a significant difference in survival on the basis of node status might be
unexpected but only 27 patients were operated on and the pathological node status of
the cohort was therefore not available. Clinical evaluation of the axilla is well
recognized to be a poor determinant of node status and ultrasound examination with
needle biopsy of any suspicious node was not practiced at the time of this study.
Given that the tumours were advanced, many of the patients who were rated Clinically
N0 (NX) would in fact have been Pathological N1 with an expected worse survival.
10
The EORTC trial10 showed that the best outcome from neoadjuvant therapy was in the
group given chemotherapy, radiotherapy and hormone treatment, as in the present
study but aromatase inhibitors and trastuzumab were not available at this time. Data
from the more recent NOAH study has shown that trastuzumab increased event free
survival in this group of patients.25 There was a survival advantage for ER positive
tumours but the difference in outcome between histological Grade 2 and less well
differentiated Grade 3 tumours was not significant.
Smoot et al20 found that
premenopausal status and palpable axillary nodes predicted poor survival in
inflammatory breast cancer but Gajdos et al2 found these trends non significant. In the
present study the only positive prognostic factor was the oestrogen receptor status but
the numbers in all these observational studies are relatively small and the risk of a type
II error for negative findings is high.
In an observational study of neoadjuvant chemotherapy followed by either surgery or
radiotherapy from the Royal Marsden 11 there was no difference in survival although
there was a non-significant increase in local recurrence in the radiotherapy group. In
the present study there has been no local recurrence in those patients having surgery
for residual disease after chemoradiotherapy but this has not impacted on survival. A
meta-analysis16 of nine randomised trials of neoadjuvant versus adjuvant chemotherapy
also shows an increased rate of local recurrence (LR) in patients treated by
neoadjuvant therapy.
It is apparent that this effect was due to non-randomised
radiotherapy without surgery in those patients with complete clinical remission in the
neoadjuvant groups and this trend was most marked in three trials.3,
9, 26
It was
concluded that neoadjuvant chemoradiotherapy should not be used without subsequent
surgery. However, we have found that provided the breast is carefully monitored and
surgery is confined to those with residual or recurrent disease, that overall survival is
11
not compromised and the incidence of uncontrolled LR is relatively low.
There was
a high mastectomy rate for residual disease in the present study 21/25 (84%) but at
least two trials have found that conservative surgery in this situation leads to a high
local recurrence rate with a secondary mastectomy rate of circa 20%.3,9
The
hypofractionation of the radiotherapy was unconventional at the time of this study but
the safety of this treatment regime has subsequently been confirmed.27
The overall survival of the patients who had subsequent surgery for local treatment failure
was not significantly better than the majority with a complete remission (Fig. 4) and there
was no disadvantage to those with a delayed operation for recurrent disease (Fig.2). In a
non-randomised observational study this non-significant finding should be viewed with
caution but it does give some reassurance that delay in offering surgery does not appear to
disadvantage patients with residual or recurrent disease, a policy which is supported by the
long-term results from the Institut Curie(28)
With an overall 5-year survival rate of 54% comparable to the published literature,
30
29,
the use of primary combined chemotherapy, radiotherapy and endocrine treatment
has been shown to provide effective treatment for locally advanced breast cancer.
However, the optimal treatment of this disease remains uncertain and the need for
further clinical studies is clear18,31 The present findings from a careful surveillance
policy, where the use of surgery was reserved for the treatment of residual disease or
local recurrence would support examination of this treatment strategy by a randomised
clinical trial.
12
Acknowledgements:
We thank Mr NJ Griffiths and Dr N Mithal for permission to include patients under
their care. We thank Vicky Stevenson for assistance with data collection.
Conflict of interest statement: None declared.
13
References
1.
Smith IE, Chua S. ABC of breast diseases. Medical treatment of early breast
cancer. IV: neoadjuvant treatment. BMJ 2006; 332: 223-224.
2.
Gajdos C, Tartter PI, Estabrook A, Gistrak MA, Jaffer S, Bleiweiss S, Ira J.
Relationship of clinical and pathologic response to neoadjuvant chemotherapy
and outcome of locally advanced breast cancer. J Surg Oncol 2002; 80: 4-11.
3.
Mauriac L, MacGrogan G, Avril A, Durand M, Floquet A, Debled M,
Dilhuydy JM, Bonichon F. Neoadjuvant chemotherapy for operable carcinoma
larger than 3cm: a unicentre randomised trial with a 124 month median followup. Bergonie Bordeau Groupe Sein.(IBBGS) Ann Oncol 1999; 10: 47-52.
4.
Feldman LD, Hortobagyi GN, Buzdar AU, Ames FC, Blumenschein GR.
Pathological assessment of response to induction chemotherapy in breast
cancer. Cancer Res 1986; 46: 2578-81.
5.
Sutherland S, Ashley S, Walsh G, Smith IE, Johnston SRD. Inflammatory
breast cancer – The Royal Marsden experience: a review of 155 patients
treated from 1990 – 2007. Cancer 2010; 116 (11 Suppl): 2815-20.
6.
Chollet P, Amat S, Cure H, de Latour M, Le Bouedec G, Mouret-Reynier MA,
Ferriere JP, Achard JL, Dauplat J, Penault-Llorca F. Prognostic significance
of a complete pathological response after induction chemotherapy in operable
breast cancer. Br J Cancer 2002; 86: 1041-6.
7.
Kell MR, Morrow M. Surgical aspects of inflammatory breast cancer. Breast
Disease. 2005-2006; 22: 67-73.
8.
De Lena M, Varini M, Zucali R, Rovini D, Viganotti G, Valagussa P, Veronesi
U, Bonnadonna G. Multimodal treatment for locally advanced breast cancer.
Results of chemotherapy-radiotherapy versus chemotherapy-surgery. Cancer
Clin trials 1981; 4: 229-236.
9.
Scholl SM, Fourquet A, Asselain B, Pierga JY, Vilcoq JR, Durand JC et al.
Neoadjuvant versus adjuvant chemotherapy in premenopausal patients
With tumours considered too large for breast conserving surgery:
preliminary results of a randomized trial: S6. Eur J Cancer 1994; 30A:
645-52
10.
Bartelink H, Rubens RD, van der Schueren E, Sylvester R. Hormonal
therapy prolongs survival in irradiated locally advanced breast cancer.
European Organization for Research and Treatment of Cancer (EORTC)
randomised phase III trial. J Clin Oncol 1997; 15: 207-15.
11.
Ring A, Webb A, Ashley S, Allum WH, Ebbs S, Gui G, Sacks NP, Walsh G,
Smith IE.
Is surgery necessary after complete clinical remission following
neoadjuvant chemotherapy for early breast cancer? J Clin Oncol 2003; 21:
4540-5.
14
12.
Pulte D, Brenner H. Changes in survival in head and neck cancers in the late
20th and early 21st century: a period analysis. Oncologist 2010; 15: 921-923.
13.
Geh JI, Bond SJ, Bentzen SM, Glynne-Jones.
Systematic overview of
preoperative (neoadjuvant) chemoradiotherapy trials in oesophageal cancer:
evidence of a radiation and chemotherapy dose response. Radiother Oncol
2006; 78: 236-244.
14.
Eifel PJ. Concurrent chemotherapy and radiation therapy as the standard of
care for cervical cancer. Nature Clin Pract Oncol 2006; 3: 248-255.
15.
Eng C, Abbruzzese J, Minsky, BD. Chemotherapy and radiation of anal
canal cancer: the first approach. Surg Oncol Clin N Am 2004; 13: 309-320
16.
Mauri D, Pavlidis N, Ioannidis A. Neoadjuvant versus adjuvant systemic
treatment in breast cancer: A meta-analysis. JNCI 2005; 97: 188-194
17.
Belluco C, De Paoli A, Canzonieri V, Sigon R, Fornasarig M, Buonadonna A et
al Long-term outcome of patients with complete pathologic response after
neoadjuvant chemoradiation for cT3 rectal cancer: implications for local
excision surgical strategies. Ann Surg Oncol 2011 Jun 21 [Epub ahead of
print]
18.
Huang EH, Tucker SL, Strom EA, McNeese MD, Kuerer HM, Hortobagyi GN
et al. Predictors of locoregional recurrence in patients with locally advanced
breast cancer treated with neoadjuvant chemotherapy, mastectomy and
radiotherapy. Int J Radiat Oncol Biol Phys 2005; 62(2): 351-357.
19.
Gonzalez-Angulo AM, Hennessey BT, Broglio K, Meric-Berstam F,
Cristofanilli M, Giordano SH et al. Trends for inflammatory breast cancer: is
survival improving? Oncologist 2007; 12: 904-912.
20.
Smoot RL, Koch CA, Degnim AC, Sterioff S, Donohue JH, Grant CS et al. A
single-centre experience with Inflammatory Breast Cancer, 1985-2003. Arch
Surg 2006; 141: 567-573.
21.
Walshe JM, Swain SM. Clinical aspects of inflammatory breast cancer.
Breast Disease 2005-2006; 22: 35-44.
22.
Cristofanilli M, Valero V, Buzdar AU, Kau SW, Broglio KR, GonzalezAngulo AM et al. Inflammatory breast cancer and patterns of recurrence:
understanding the biology of a unique disease. Cancer 2007; 110: 1436-44.
23.
Montagna E, Bagnardi V, Rotmensz N, Rodriguez J, Veronesi P, Luini A et
al. Factors that predict early treatment failure for patients with locally
advanced (T4) breast cancer. Br J Cancer 2008; 98: 1745-1752.
15
24.
Dawood S, Ueno NT, Valero V, Woodward WA, Bucholz TA, Hortobagyi
GN, Gonzalez-Angulo AM, Cristofanilli M. Differences in survival among
women with stage III inflammatory and non-inflammatory locally advanced
breast cancer appear early: a large population-based study. Cancer 2011; 117:
1819-1826
25.
Semiglazov V, Eiermann W, Zambetti M et al. Surgery following neoadjuvant
therapy in patients with HER2-positive locally advanced or inflammatory
breast cancer partcipating in the NeOAdjvant Herceptin (NAOH) study. Eur J
Surg Oncol. In press. Available on line 16th August 2011.
26.
Gazet JC, Ford HT, Gray R, McConkey C, Sutcliffe R, Quilliam J, et al.
Estrogen-receptor-directed neoadjuvant therapy for breast cancer: results of a
randomized trial using formestane & methotrexate, mitozantrone &
mitomycin C (MMM) chemotherapy. Ann Oncol 2001; 12: 685-691.
27.
The START Trialists’ Group. The UK Standardisation of Breast Radiotherapy
(START) Trial B of radiotherapy hypofractionation for treatment of early
breast cancer: a randomised trial. Lancet 2008; 371 (9618): 1098-1107.
28.
Abrous-Anane S, Savignoni A, Daveau C, Pierga JY, Gautier C, Reyal F et al.
Management of inflammatory breast cancer after neoadjuvant chemotherapy.
Int J Radiat Oncol Biol Phys 2011; 79: 1055-1063.
29.
Therasse P, Mauriac L, Welnicka-Jaskiewicz M et al. Final results of a
randomised Phase III trial comparing cyclophosphamide, Epirubicin and
Fluorouracil with a dose intensified epirubicin and cyclophosphamide +
Filgrastim as neoadjuvant treatment in locally advanced breast cancer: An
EORTC-NCIC-SAKK multicentre study. J Clin Oncol 2003; 21: 843-850.
30.
Bristol IJ, Woodward WA, Strom EA, Eric A, Cristofanilli M, Domain D et al.
Locoregional treatment outcomes after multimodality management of
inflammatory breast cancer. Int J Rad Oncol Biol Phy. 2008; 72; 474-484.
31.
Sinacki M, Badzio A, Welnicka-Jaskiewicz M, Bogaerts J, Piccart M, Therasse
P. et al. Pattern of care in locally advanced breast cancer: Focus on local
therapy. The Breast 2011; 20: 145-150.
16
Tables and Figures.
Table 1.
Tumour Characteristics.
Fig.1
Treatment Outcome of the Cohort.
Fig.2
Surgery for Residual v Recurrent Disease
Fig.3
Overall Survival: Surgery v No Surgery
Fig.4
Survival of Total Cohort.
Fig.5b
Survival by TNM Stage.
17
Table 1.
Tumour Characteristics (n=123)
Tumour
Number of Cases
T2 > 3 cm
24
T3 > 5 cm
39
T4b diffuse (peau d'orange)
31
T4d inflammatory (erythema)
29
Clinical Node Status
No
79
N1
44
pNx (AJCC)
123
Distant metastasis
Grade
M0
123
I
2*
II
41
III
59
NR
21
ER Status +ve
50
-ve
56
NR
17
Tumour Type
Invasive ductal ca.
101
Invasive lobular ca.
14
Mixed IDC /ILC.
3
Carcinosarcoma
3
Medullary ca.
1
NR
1
*Both T4 tumours confirmed on review of grade. NR: Not recorded
18
19
Fig. 1
Treatment Outcome of Cohort of Patients with Locally
Advanced or Inflammatory Breast Cancer
Total Cohort
n = 123
Complete Clinical & Biopsy Response
Residual or Progressive Disease
n = 80
n = 43
Operable Local
Recurrence
Complete Response
No Surgery
Operable Residual
Disease
Progressive Disease
No Surgery
n = 12
n = 68
n = 25
n = 18
Further Local
Recurrence
n = 5 (RRx1)
Subsequent
Unoperated Local
Recurrence
n =12(RRx3),)
Local Recurrence
Nil
Residual Disease
n = 18 (RRx2)
Poorly controlled
local disease
n=7
RR=Regional recurrence
20
Fig.2
Surgery for Residual v Recurrent Disease
4= Residual Disease, 5=Recurrent
P=0.65 HR 1.31 (0.42-3.95)
21
Fig. 3
Overall Survival: Surgery v No Surgery
1= Complete Remission- No Surgery,
2= Surgery for Residual or Recurrent Disease
p = 0.218 HR 1.47 95% CI (0.81-2.55)
22
Fig. 3a
Survival by Clinical Node Status
P=0.28 95% CI (0.4 - 1.3)
23
Fig. 4
Survival Total Cohort
1. Complete Remission (CR) at Assessment – No Surgery
3. Progressive Disease – No Surgery
4. Residual Disease at Assessment – Surgery
5. Recurrent Local Disease post CR - Surgery
24
Replace by Fig 5b
25
Fig 5b
Survival by TNM Stage
26